The compounds 2,2-diorgano-3-arylpropionic acids are known compounds which are used as intermediates in the production of pharmaceuticals and herbicides. For example, 2,2-dialkyl-3-phenylpropionic acids are intermediates for the production of 2,2-dialkyl-1-indanones. An example of such preparation includes the preparation of 2,2-dimethyl-1-indanone by treating 2,2-dimethyl-3-phenylpropionic acid with a Lewis acid such as anhydrous hydrogen fluoride. 2,2-Dialkyl-1-indanones such as 2,2-dimethyl-1-indanone and 2,2-diethyl-1-indanone are valuable intermediates in the pharmaceutical industry. For example, 2,2-dimethyl-1-indanone is used in the synthesis of antiallergic agent 4-(6'-chloro-2',2'-dimethylinden-1'-ylidene)-1-methylpiperidine, the anti-inflammatory and anti-arthritic indane-5-acetic acid derivatives disclosed in U.S. Pat No. 4,166,131, and other bioactive compounds such as coumarins. Furthermore, the 2,2-diorgano-3-arylpropionic acids produced in accordance with the present invention, for example, 2,2-dialkyl-3-phenylpropionic acids and, more particularly, 2,2-dimethyl-3-phenylpropionic acids, are valuable intermediates for the production of antibiotics, cardiovascular agents, anticholesterimic agents and herbicides.
2,2-Diorgano-3-arylpropionic acids have been prepared in the past by several different methods. Nichols et al., Effects of Certain Hallucinogenic Amphetamine Analogues on the Release of [3'] Serotonin from Rat Brain Synaptosomes, J. Med. Chem., 25, 530-535 (1962) discloses the preparation of 2,2-dimethyl-3-(4-methoxyphenyl)propionic acid and 2,2-dimethyl-3-[3,4-(methylenedioxyl)phenyl]propionic acid.
Carbonylation of alcohols to form acids has been used in the past. For example, Japanese Kokai Patent No. SHO 55[1980]-27147, published on Feb. 27, 1980, discloses the preparation of 2-(4'-isobutyl-phenyl)propionic acid by reacting 2-(4'-isobutyl-phenyl)ethanol with carbon monoxide and water in the presence of hydrogen fluoride. In that process, like in other prior processes involving a Koch reaction, the carboxyl group forming the acid was bonded to the same carbon atom that the hydroxyl group of the reactant alcohol was bonded to prior to the carbonylation.
U.S. Pat. No. 4,981,995 discloses the preparation of 2-(4'-isobutylphenyl)propionic acid by carbonylating 1-(4'-isobutylphenyl)ethanol with carbon monoxide in an acidic aqueous medium using a palladium complex. A small amount of 3-(4'-isobutylphenyl)propionic acid is formed as a byproduct involving the bonding of the carboxyl group to a carbon which is not the same as the carbon that the hydroxyl group of the reactant alcohol is bonded to prior to the carbonylation. This shift of the carbonylation to a different carbon atom is attributed to the presence of the transition metal catalyst, i.e., the palladium complex.
U.S. Pat. No. 5,012,007 discloses the preparation of a propionic acid and, more particularly, 2,2,dimethyl-3-(4'-methoxyphenyl)propanoic acid by carbonylating 1,(4'-methoxyphenyl)-2-methyl-1-propanol in the presence of hydrogen fluoride at room temperature in a reactor pressurized to 450 psig with carbon monoxide. The reaction also produced a larger amount of 6-methoxy-2,2-dimethyl-1-indanone. In that patent, the reactant carbinols are characterized by the fact that at least one of the ring carbons which is in a position adjacent to the 1-position of the ring is bonded to a hydrogen. That together with the temperature of the reaction cause the cyclization of the reactant to form the indanone.
Other than the specific and limited disclosure of U.S. Pat. No. 5,012,007, none of the above referenced or any other prior process disclose the preparation of 2,2-diorgano-3-arylpropionic acids from corresponding 2,2-diorgano-1-arylethanol by carbonylating such carbinols in the presence of a Lewis acid catalyst. The present invention discloses such process.
2,2-Diorgano-3-arylpropionic acid esters have been prepared in the past by reacting an aryl chloride with methyl isobutyrate in the presence of a base. Warrich et al., The Migration Aptitude of Benzyl vs. Methyl in Carbonium Ion Reaction of the 2,2-dimethyl-3-phenyl-1-propyl System, J. Am. Chem. Soc., 4095-4100 (1962) describes the reaction of benzyl chloride with methyl isobutyrate in the presence of a base such as sodium hydride to form 2,2-dimethyl-3-phenylpropionic acid methyl ester. U.S. Pat. No. 4,166,131 discloses the preparation of 2,2-dimethyl-3-(4'-chlorophenyl)propionate by reacting 4-chlorobenzyl chloride with methyl isobutyrate in the presence of a base such as sodium hydride. None of these processes discloses the preparation of 2,2-diorgano-3-arylpropionic acid esters from corresponding 2,2-diorgano-1-arylethanol by the carboalkoxylation in the presence of a Lewis acid catalyst.
These and other objects and advantages of the present invention will become apparent from the following description.